Aerosols for sinunasal drug delivery

Inactive Publication Date: 2007-08-30
PARI PHARMA GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009] In a first principal aspect, the invention provides an aerosol for delivering an active compound to the mucosa of the nose or of a paranasal sinus. The aerosol comprises a dispersed liquid phase and a continuous gas phase. The volume of the dispersed liquid phase w

Problems solved by technology

These conditions may be associated with significant symptoms and have a negative impact on quality of life and daily functioning.
On the other hand, the effective treatment of the nasal and paranasal mucosa remains challenging.
While the mucosa of the nasal cavity is a feasible target for locally administered drugs formulated as nasal sprays, the sinuses are not easily accessed by liquid formulations.
However, it has been found by the inventors that these teachings of the prior art do not actually ensure the deposition of a large fraction on the sinunasal mucosa, depending on the actual configuration of the devices and the aerosol characteristics.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Comparative Example

[0169] A commercial aqueous suspension formulation of fluticasone-17-propionate (Flutide® forte Fertiginhalat 2,0 mg / 2 ml) was nebulised with an aerosol generator (SinuNEB™) which has been suggested for the delivery to the paranasal sinuses. The sinunasal deposition of the aerosol was evaluated in an in vitro model.

[0170] Sinunasal deposition model. A cast model based on the anatomical shapes and dimensions of the nasal cavity and the nasal passage was built from plastic. In this model, the paranasal sinuses are simulated by 6 exchangeable glass bottles, 3 on either side, representing the frontal, maxillary, and sphenoid sinuses, respectively. Exchangeable, artificial ostiae of 10 mm length were used to connect the artificial sinus cavities to the nose model. Moreover, the model has two openings representing artificial nostrils and one opening for the simulation of the pharynx which connects the nasal cavity with the trachea. The deposition model is also equippe...

example 2

Comparative Example

[0176] To exclude the possibility that an aqueous suspension such as Flutidee forte—even though the product is approved for administration by inhalation using a jet nebuliser—is particularly unsuitable for aerosol delivery to the sinuses, the experiment of Example 1 was repeated with a different formulation of fluticasone-17-propionate. In this case, the test formulation was an experimental aqueous solution which contained 455 μg of the drug in the charged volume of 2.0 ml. Gamma-cyclodextrin (50 mg / ml) was incorporated to solubilise the poorly water-soluble active ingredient. Further inactive ingredients were sodium chloride (9 mg / ml) and hydrochloric acid (to pH 6). The dynamic viscosity of the solution was 1.14 mPa·s, the surface tension 71.6 mN / m.

[0177] In result, the relative amount of drug remaining in the nebuliser was lower (about 56% of the charged dose) and the inhaled fraction was higher (about 16.2%) than in the case of Flutidee forte. However, the d...

example 3

[0178] In another experiment, the same sinunasal deposition model and the same test formulation as in Example 1 were used, but a different aerosol generator. Thus, instead of a SinuNEB® aerosol generator, a VibrENT® apparatus was used, which is a jet nebuliser similar to the PARI LC Star®, but adapted to deliver an aerosol into a nostril, in combination with a compressor (PARI SINUS) designed to deliver compressed air whose pressure pulsates at a frequency of 30 to 60 Hz. A frequency of 44 Hz was selected.

[0179] Another difference was that the nosepiece of the nebuliser was connected with one of the nostrils at a time, and that the other nostril was closed with a flow resistor. Aerosol, coming out of the exit nostril was captured on a filter. The artificial pharynx was closed, taking into account that the VibrENT® aerosol generator is intended for nasal inhalation with the soft palatine being in the closed position, thus separating the sinunasal space from the lower respiratory tra...

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Abstract

A pharmaceutical aerosol is disclosed which is suitable for delivering an active compound to the mucosa of the nasal cavity or of the paranasal sinuses. The aerosol is characterised in that its pressure is not constant, but pulsates at a frequency of about 10 to 90 Hz. The mass median diameter of the dispersed phase is from about 2 to 6 μm, and the volume of about 5 mL or less of the dispersed phase comprises a unit dose of an active compound. The aerosol is, inter alia, suitable for the prevention, management, or treatment of a disease, symptom, or condition affecting the nose or the paranasal sinuses, such as acute and chronic sinusitis.

Description

FIELD OF THE INVENTION [0001] The present invention is related to pharmaceutical aerosols and to liquid compositions which are suitable for aerosolisation. In further aspects, the invention relates to therapeutic uses of aerosols and to methods of producing them and of administering them to patients. The aerosols are suitable for delivering drug substances to selected regions within the respiratory tract, including the nasal cavity and the paranasal sinuses. BACKGROUND OF THE INVENTION [0002] Diseases and conditions affecting either paranasal sinuses or both the nasal cavity and the paranasal sinuses, in particular acute and chronic forms of rhinosinusitis, are increasing in incidence and prevalence in many countries and regions of the world, including Europe and the United States. These conditions may be associated with significant symptoms and have a negative impact on quality of life and daily functioning. [0003] On the other hand, the effective treatment of the nasal and paranas...

Claims

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Application Information

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IPC IPC(8): A61K9/12A61K31/573A61K38/00A61K31/724A61K31/717A61K9/127
CPCA61K9/0043
InventorSCHUSCHNIG, UWE
OwnerPARI PHARMA GMBH